Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Cabibbo, Giuseppe; Celsa, Ciro; Calvaruso, Vincenza; Petta, Salvatore; Cacciola, Irene; Cannavò, M.R.; Madonia, Salvatore; Rossi, M.; Magro, Bianca; Rini, Francesca; Distefano, Marco; Larocca, Licia; Prestileo, Tullio; Malizia, Giuseppe; Bertino, Gaetano; Benanti, F.; Licata, Anna; Scalisi, I.; Mazzola, Giovanni; Rosolini, Maria Antonietta Di; Alaimo, Giuseppe; Averna, A.; Cartabellotta, F.; Alessi, Nicola; Guastella, Salvatore; Russello, Maurizio; Scifo, G.; Squadrito, Giovanni; Raimondo, Giovanni; Trevisani, Franco; Marco, V. Di; Cammà, Calogero; Hcv, Rete Sicilia Selezione Terapia –

doi:10.1016/j.jhep.2019.03.027

Cited by 153 publications

(99 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The tertiary prevention effect of DAA was momentary during antiviral therapy (Frame II) and diminished after the end of treatment, as seen in Supplementary Figure S1B,E. The HCC recurrence rate in the DAA treated arm was not higher than the untreated arm (DAA vs. untreated: 5602.4 vs. 6734.6/10 4 person-years, log-rank p = 0.135), echoing recent studies' findings [23][24][25]. In contrast, the tertiary prevention effect of the Peg-IFN/RBV regimen was sustained throughout the antiviral therapy and even after EOT, showing a significantly lower recurrence rate than the untreated and DAA arms, as seen in Table 1, Supplementary Figure S1C,F.…”

Section: Discussionsupporting

confidence: 74%

“…However, a recent meta-analysis concluded that the HCC occurrence and recurrence rates were comparable between DAA-and IFN-treated patients regardless of the higher SVR rate of the DAA regimen [10]. Moreover, several reports with single-arm DAA-treated HCV-HCC patients declared abruptly increased HCC recurrence rate after antiviral treatment [11][12][13][14], while conflicting results have been reported in other studies comparing to the untreated [15][16][17][18][19][20][21][22][23][24][25] or IFN-treated groups [10,21,[26][27][28][29][30]. Concerns have been raised about the benefit and the timing of adjuvant DAA-based therapy.…”

Section: Introductionmentioning

confidence: 99%

“…Some of these studies consisted of an IFN-containing DAA regimen [27,28] and did not adjust for baseline characteristics before comparison [26,30]. The definition of follow-up duration varies across these studies [10,21,[23][24][25][26][27][28][29][30] and may lead to inconsistent or conflicting comparison results [31]. We therefore conducted this nested case-control study, using propensity score matching (PSM) to adjust for the confounders, and with application of different follow-up time frames to investigate if the tertiary prevention effect is different between the DAA and PegIFN/RBV regimens in curative CHC-HCC patients.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma

Teng

Jeng

Yang

et al. 2019

Cancers

View full text Add to dashboard Cite

The elimination of chronic hepatitis C infection (CHC) by pegylated interferon plus ribavirin (Peg-IFN/RBV) decreases hepatocellular carcinoma (HCC) recurrence rate. However, the tertiary prevention of HCC recurrence by direct acting antiviral agents (DAA) remains controversial. This study aims to compare the tertiary prevention effect between DAA and Peg-IFN/RBV in CHC-HCC patients. Three hundred and one patients who received curative HCC treatment were retrospectively recruited. The recurrence incidence rate (IR) was compared among patients either receiving Peg-IFN/RBV or DAA regimen or untreated by three timeframes (I: from HCC treatment to antiviral therapy; II: during antiviral therapy; III: after antiviral therapy). The prevention effect between Peg-IFN/RBV and DAA were compared in frame II and III after propensity score matching (PSM) with age, tumor staging, HCC treatment modality, and cirrhotic status. Before PSM, the recurrence IRs in three arms were comparable in frame I, while being lower in the Peg-IFN/RBV and DAA arm compared to the untreated arm in frame II. In frame III, the tertiary prevention effect lasted in the Peg-IFN/RBV arm (p < 0.001), but diminished in the DAA arm (p = 0.135) compared to untreated patients. After PSM, the HCC recurrence IR was higher in the DAA arm than the Peg-IFN/RBV arm in frame II (2724 vs. 666 per 10 4 person-years, log-rank p = 0.042) and III (5259 vs. 3278 per 10 4 person-years, log-rank p = 0.048). Preantiviral ALBI grade therapy is the only predictor for postantiviral therapy HCC recurrence. In conclusion, the tertiary prevention effect of HCC recurrence was not durable in DAA-treated patients, but persisted in Peg-IFN/RBV treatment patients.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma

Teng

Jeng

Yang

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…Current molecular markers of liver cancer, such as α-fetal protein [4], decarboxylation of thrombin [5] and insulin-like growth factor [6] cannot clearly distinguish between liver cancer and liver cirrhosis. Additionally, treatment of early hepatocellular carcinoma can improve the survival rate of patients [7]. Therefore, it is very important to understand the mechanism by which liver cirrhosis develops into liver cancer, and explore the molecular characteristics of HCC occurrence, development, and poor prognosis to provide new strategies for the effective prevention, diagnosis and treatment of HCC.…”

mentioning

confidence: 99%

Bioinformatics-based screening of key genes for transformation of liver cirrhosis to hepatocellular carcinoma

Chen

Yuan

et al. 2020

J Transl Med

View full text Add to dashboard Cite

Background: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms.Methods: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Results:In total, 58 DEGs were obtained, of which 12 and 46 were up-and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes.Conclusion: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.

show abstract

“…( 7‐10 ) Other authors described a higher incidence of tumor recurrence after curative therapies for HCC, particularly with more aggressive tumor patterns, ( 6,11 ) whereas other groups reported no association. ( 12‐17 ) Consequently, whether rapid viral eradication with DAAs leads to an abrupt withdrawal of antineoplastic immunological surveillance is still under discussion. ( 18 )…”

mentioning

confidence: 99%

Direct‐Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait‐List Progression or Posttransplant Recurrence

et al. 2020

View full text Add to dashboard Cite

The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre-or post-LT DAA effect). From 994 included patients, 50.6% were HCV−, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alphafetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre-or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT. LiverTransplantation 26 640-650 2020 AASLD. PiñerO et al. liver transPlantatiOn, vol. 26, no. 5, 2020 PiñerO et al.

show abstract

Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Cited by 153 publications

References 42 publications

Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma

Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma

Bioinformatics-based screening of key genes for transformation of liver cirrhosis to hepatocellular carcinoma

Direct‐Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait‐List Progression or Posttransplant Recurrence

Contact Info

Product

Resources

About